Functional magnetic resonance imaging (fMRI) based on blood oxygen level dependent (BOLD) has become one of the most powerful neuroimaging techniques for mapping brain activity in humans. The magnitude of BOLD contrast is determined by hemodynamic changes, such as cerebral blood flow (CBF) and cerebral blood volume (CBV), and the metabolic change of cerebral oxygen consumption rate (CMR/02). However, the quantitative relationships between these parameters and the BOLD phenomenon or the fundamental physiologic relationships between these parameters and increased neuronal activity are not thoroughly understood. Especially controversial are the questions of how much CMR02 is elevated during neuronal activity and whether the CMR/02 increase matches the change of CBF or cerebral glucose consumption rate (CMRglc). The long-term objective of this project is to quantitatively determine the dynamic relationships of metabolic and hemodynamic changes in response to neuronal activity in the human brain using the unique capabilities of the nuclear magnetic resonance (NMR) methodology. We propose to use MR imaging methods to quantitatively map CBF and BOLD changes in the human brain during increased focal neuronal activity and magnetic resonance spectroscopy (MRS) techniques to determine CMRO2, CMRglc and other metabolic changes in the region of increased activity in single subjects. The specific aims are: (1) To simultaneously determine and quantify the correlation between dynamic CBF and BOLD changes during graded and prolonged visual stimulation using newly-developed fMRI techniques and to examine the neuronal behavior during prolonged stimulation; (2) to improve multiple-nucleus single-bolume MRS techniques for determining metabolic changes of CMRO2 CMRglc, total adenosine triphosphate (ATP) turnover and lactate production between resting condition and functional stimulation; (3) to determine and compare the CMR02, CBF and BOLD changes in response to two different visual stimuli presented at the left and right hemifields, respectively; and (5) to validate the feasibility of using functional CBF and BOLD maps to create functional CMR02 maps. The results of these experiments will provide new information on (i) the underlying mechanism of the hemodynamic and metabolic responses during elevated neuronal activity and (ii) the quantitative relationship between the signal changes detected by fMRI and the degree of neuronal activity in normal subjects.